三阴性乳腺癌(triple-negative breast cancer,TNBC)缺乏ER/PR/HER2靶点,表现出高度侵袭性,并与不良预后相关。肿瘤浸润B细胞(tumor-infiltrating B-cells,TIL-B)已被认为是抗肿瘤免疫与免疫逃逸的关键调控者之一,但其在TNBC中的具体作...三阴性乳腺癌(triple-negative breast cancer,TNBC)缺乏ER/PR/HER2靶点,表现出高度侵袭性,并与不良预后相关。肿瘤浸润B细胞(tumor-infiltrating B-cells,TIL-B)已被认为是抗肿瘤免疫与免疫逃逸的关键调控者之一,但其在TNBC中的具体作用及对免疫检查点抑制剂(immune checkpoint inhibitors,ICI)疗效的影响尚未完全阐明。对GEO数据库中2个TNBC单细胞RNA测序数据进行分析,用于识别并注释TIL-B亚群。通过无监督聚类将样本分为“激活型”和“抑制型”B细胞组。在TCGA-TNBC队列中比较2组B细胞的免疫浸润、细胞间通讯网络及生存差异,并在独立GEO队列中进行验证。采用LASSO与Cox回归筛选关键预后基因,并构建四基因风险模型。激活型B细胞组表现出显著增强的细胞间免疫信号、更高水平的CD8^(+)T细胞与NK细胞浸润,以及改善的总体生存率(P=0.016)。由JCHAIN、F11R、IGHG3与CD24构成的预后模型在TCGA队列中分别实现了1、3和5年生存预测的AUCs为0.82、0.72和0.81,并在独立数据集中得到了稳健验证。通过对TNBC中B细胞激活状态的前瞻性描绘,揭示了其在抗肿瘤免疫及ICI应答中的潜在作用。四基因预后风险模型为个体化免疫治疗决策及B细胞靶向干预提供了有力工具。展开更多
The chronological and morphological changes of the nucleus during mouse oocyte maturation and fertilization were systematically studied. Although most oocytes went through GVBD 2-4 hrs after culture, 13.6% remained at...The chronological and morphological changes of the nucleus during mouse oocyte maturation and fertilization were systematically studied. Although most oocytes went through GVBD 2-4 hrs after culture, 13.6% remained at GV stage 8 hrs after culture.TEM observation revealed that nucleoli of oocytes which failed to go through GVBD were composed of fibrillar-granular component,small vacuoles and fibrillar centers or showed small vacuoles on nuclear surface. During GVBD, the nucleoli became smaller and smaller and finally disappeared with the nuclear-associated chromatin dislocated to the periphery. Nuclear membrane with attached chromatin became folded and electronic dense cores appeared in the center of chromatin clumps at the same time.The last event of GVBD was the disruption of nuclear membrane.At the end of the 5th hr after culture, meiosis progressed to prometaphase I.Chromosomes,distributed in the original GV area free of organelles,were surrounded by large quantity of mitochondria and small SER vesicles. At the end of the 12th hr after culture,48. 1% of the oocytes emitted PB1.Decondensing sperm head and early male pronuclcus(mPN)with condensed nucleoli were found 1-2 hrs after insemination.The formation and enlargement of female PN(fPN) occurred a little earlier than that of mPN. 33.3% finished syngamy at 8-9 hrs after insemination.The process of nucleolus formation was reverse to that in GVBD. The oolemma modification caused by cortical reaction could effectively inhibit polyspermy.in contrast,there were sperm binding to the oolemma where CGs failed to be released. In addition, PB2 was emitted 2-5 hrs after insemination. The difference between PB1 and PB2 as well as the abstriction of polar body were also discussed.展开更多
文摘The chronological and morphological changes of the nucleus during mouse oocyte maturation and fertilization were systematically studied. Although most oocytes went through GVBD 2-4 hrs after culture, 13.6% remained at GV stage 8 hrs after culture.TEM observation revealed that nucleoli of oocytes which failed to go through GVBD were composed of fibrillar-granular component,small vacuoles and fibrillar centers or showed small vacuoles on nuclear surface. During GVBD, the nucleoli became smaller and smaller and finally disappeared with the nuclear-associated chromatin dislocated to the periphery. Nuclear membrane with attached chromatin became folded and electronic dense cores appeared in the center of chromatin clumps at the same time.The last event of GVBD was the disruption of nuclear membrane.At the end of the 5th hr after culture, meiosis progressed to prometaphase I.Chromosomes,distributed in the original GV area free of organelles,were surrounded by large quantity of mitochondria and small SER vesicles. At the end of the 12th hr after culture,48. 1% of the oocytes emitted PB1.Decondensing sperm head and early male pronuclcus(mPN)with condensed nucleoli were found 1-2 hrs after insemination.The formation and enlargement of female PN(fPN) occurred a little earlier than that of mPN. 33.3% finished syngamy at 8-9 hrs after insemination.The process of nucleolus formation was reverse to that in GVBD. The oolemma modification caused by cortical reaction could effectively inhibit polyspermy.in contrast,there were sperm binding to the oolemma where CGs failed to be released. In addition, PB2 was emitted 2-5 hrs after insemination. The difference between PB1 and PB2 as well as the abstriction of polar body were also discussed.
